Mood-altering drugs are the most frequently prescribed medications in the United States. They include MAO inhibitors (MAOI), selective serotonin reuptake inhibitors (SSRI), phenothiazines, tricyclic antidepressant drugs, and drugs of abuse such as cocaine. MAOIs, which include isocarboxazid (Marplan), phenelzine (Nardil), pargyline (Eutonyl), tranylcypromine (Parnate), and deprenyl, bind irreversibly to the enzyme MAO, thereby increasing intraneuronal levels of amine neurotransmitters (serotonin, norepinephrine, dopamine, epinephrine, octopamine). This increase is associated with an antidepressant effect, an antihypertensive effect, an antinarcoleptic effect, liver enzyme elevation, and delayed onset of Parkinson disease (deprenyl). 508 Because two forms of the enzyme (MAO-A and MAO-B) are selective in vitro for substrate (MAO-A is selective for serotonin, dopamine, and norepinephrine; MAO-B for tyramine and phenylethylamine), presumably MAOIs selective for MAO-A or MAO-B would have different effects. 817 This is not known for certain, as deprenyl (selegiline, Eldepryl), an MAOI-Bselective drug, improves a dopamine deficiency state, parkinsonism. 508

Interactions between MAOIs and a variety of foods and drugs containing indirect-acting sympathomimetic substances such as ephedrine or tyramine (found especially in aged cheeses) can occur for as long as 2 weeks after the last dose of MAOI is given. The most serious effects of this interaction are convulsions and hyperpyrexic coma (particularly after narcotics).

Anesthetic management of a patient given an MAOI can be chaotic: For this reason it is widely accepted practice to discontinue MAOIs at least 2 to 3 weeks before any planned operation. 818,819,820,821,822,823,824,825,826,827,828 An alternate point of view has recently been expressed regarding severely psychotic patients or emergency surgery. 817,829,830 Clearly, the risk of discontinuing MAOIs must be weighed against the risk of suicidal tendencies in some patients deprived of MAOIs. There are no reported experiences of interactions between narcotics and deprenyl, so judgments about possible worsening of Parkinson disease and continuing MAOIs have no basis in data. It should be noted that severe reactions have occurred when too short an interval existed between administration of MAOIs and tricyclic antidepressants. 705 Emergency surgery on patients given MAOIs can be punctuated by hemodynamic instability. Regional block can be attempted as treatment for postoperative pain to avoid having to give narcotics. Case reports of hyperpyrexic coma following administration of most narcotics exist for humans, and animal studies document a 10 to 50 percent incidence of hyperpyrexic coma in animals pretreated with MAOIs and then given a variety of narcotics. 818,819,820,821,822,823,824,825,826,827,828 These reactions appear to be best treated using therapy supporting vital functions.

Alternate drugs for the treatment of severe depression include the tricyclic antidepressant drugs: amitriptyline (Elavil, Endep), imipramine (Imavate, Tofranil, Presamine), despiramine (Norpramine), doxepin (Adapin, Sinequan), nortriptyline (Aventyl), fluoxetine (Prozac), trazodone (Desyrel), and bupropion (Wellbutrin). 823 Tricyclic antidepressant drugs also block the reuptake of neurotransmitters and cause their acute release. Given chronically, these drugs decrease the stores of noradrenergic catecholamines. Tricyclic antidepressant drugs also produce side effects similar to those of atropine (dry mouth, tachycardia, delirium, urinary retention) and can cause changes on ECG (changes in T wave, prolongation of the QRS complex, bundle branch block or other conduction abnormalities, or premature ventricular contractions). Although arrhythmias induced by tricyclic antidepressants have been treated successfully with physostigmine, bradycardia has sometimes occurred. 823 Drug interactions with tricyclic antidepressants include those related to blockade of the reuptake of norepinephrine (such as interference with the action of guanethidine) and fatal arrhythmias after halothane and pancuronium. 831,832,833 Such interactions, although predictable for a population of patients, may not alter a patients threshold for arrhythmias. The newer antidepressants (the SSRIs) also have serious side effects. Fluoxetine, a tricyclic that also has an SSRI effect, causes nausea, vomiting, headaches, nervousness, and possibly paranoia and ideas of suicide more commonly than do the other tricyclics 823 but is less likely to cause anticholinergic effects or orthostatic hypotension. Bupropion may cause nausea, vomiting, seizures, agitation, tremor, excitement, and increased motor activity but only rarely causes anticholinergic effects or orthostatic hypotension. Switching between drugs for depression can cause hyperpyrexia and coma. Thus, switching prior to surgery should not be requested casually. 823

The effectiveness of phenothiazines and butyrophenones in schizophrenia suggests a dopamine receptorblocking action. In addition, these drugs possess varying degrees of parasympathetic stimulation and ability to block a-adrenergic receptors. The phenothiazines include chlorpromazine (Thorazine, Chlor-PZ), promazine (Sparine), triflupromazine (Vesprin), fluphenazine (Prolixin), trifluoperazine, prochlorperazine (Compazine), and many others. The butyrophenones include droperidol and haloperidol (Haldol). Both phenothiazines and butyrophenones produce sedation, depression, and antihistaminic, antiemetic, and hypothermic responses. They are also associated with cholestatic jaundice, impotence, dystonia, and photosensitivity. Other side effects associated with phenothiazines include orthostatic hypotension (partly due to a-adrenergic blockade) and ECG abnormalities, such as prolongation of the QT or PR intervals, blunting of T waves, depression of the ST segment, and, on rare occasion, PVCs and torsades de pointes. 823,832,833 Although few data are available on the antidepressant drugs selective for serotonin (the SSRIs), occasional case reports of severe hypotension and cardiac arrest with severe bradycardia have been presented in abstract form.

Several important drug interactions are noteworthy for the phenothiazine derivatives. The effects of CNS depressants (especially narcotics and barbiturates) are enhanced by concomitant administration of phenothiazines. Also, CNS seizure threshold is lowered by administration of phenothiazines, which should be avoided in patients who are epileptic or withdrawing from any drug that depresses the CNS. The antihypertensive effects of guanethidine and guanadrel are blocked by tricyclic antidepressant drugs and phenothiazines. 786 Lithium carbonate is used to treat manic depression; it is more effective in preventing mania than in relieving depression. In excitable cells, lithium mimics sodium, decreasing the release of neurotransmitters both centrally and peripherally. Lithium prolongs neuromuscular blockade 834 and may decrease anesthetic requirements because it blocks brain-stem release of norepinephrine, epinephrine, and dopamine.

Psychoactive drugs such as amphetamines (including methamphetamines and their smokable derivative in crystal form, known as ice) and cocaine acutely release norepinephrine, epinephrine, and dopamine and block their reuptake. Taken chronically, they deplete the nerve endings of these neurotransmitters.

Drugs that appear to increase central a-adrenergic release increase anesthetic requirement, whereas drugs that appear to decrease central a-adrenergic release decrease anesthetic requirements. (This may not be the mechanism by which they alter anesthetic requirement, but it is a convenient way of remembering the alteration.) Drugs that affect only the b-adrenergic receptors do not alter anesthetic requirements. 167,168,217,795,796,835,836